A Phase II Trial to Evaluate the Efficacy of AZD6094 (HMPL-504) in Patients With Papillary Renal Cell Carcinoma (PRCC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Trial to Evaluate the Efficacy of AZD6094 (HMPL-504) in Patients With Papillary Renal Cell Carcinoma (PRCC) (NCT02127710), a na phase 2 study. The primary outcome is Objective Response Rate (RECIST Version 1.1).

2. Clinical Question

The registry describes an efficacy and safety evaluation, not a randomized test of AZD6094 against another treatment or against a concurrent control. The primary endpoint is objective response rate (ORR). It focuses on whether measurable tumors meet criteria for complete or partial response, as judged by the investigator.

Because the primary analysis set required measurable disease, central confirmation of PRCC, and receipt of at least 1 dose, the endpoint does not automatically describe every person enrolled. The registry record reports enrollment of 111, while the stated efficacy analysis set is n = 85. Those figures refer to different trial populations and should not be treated as interchangeable.

The central clinical-statistical question is therefore descriptive: how often a qualifying response was observed in the defined analysis set under the trial's assessment approach. The registry record does not report the response count, response proportion, confidence interval, or a statistical comparison for this endpoint. It therefore does not permit a conclusion about the observed magnitude or precision of ORR.

3. Trial Design

This was a completed, open-label, single-arm, multicentre, global phase II study sponsored by AstraZeneca. The registry lists enrollment of 111 and describes AZD6094 as the intervention. Participants received 600 mg by mouth once daily, continuously. The study included patients with PRCC who were treatment naïve or previously treated.

With a single group and no masking, treatment and outcome assessment were not blinded through a comparison structure. The primary endpoint was assessed by investigator review under RECIST version 1.1. The study description also says that an independent central pathology review would confirm PRCC, while locally available pathology results could be used to allow timely study entry. The primary efficacy analysis set, in turn, was defined to include measurable disease, central laboratory confirmation, and at least 1 dose.

The registry lists the study as completed, with a start date of 2014-04-30 and primary completion on 2016-04-14. Completion indicates the registry's recorded status; it does not by itself establish that every planned analysis or result is available in the record. The registry lists 18 outcome measures, including ORR as the primary measure and secondary outcomes addressing progression-free survival, overall survival, tumor-size change, duration of response, and peak plasma concentration. Several survival outcomes were specified by c-MET status and analysis set.

Allocation is recorded as NA, consistent with a single-group design rather than assignment between trial arms. The registry record does not report a concurrent comparator, a randomized allocation procedure, or masking. The sample-size justification and detailed statistical analysis plan are not reported in the registry record. Consequently, the design supports a description of observed outcomes in the treated cohort, but it does not provide a randomized estimate of comparative treatment effect.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: All patients were required to provide an archived or fresh tumour sample at enrolment to confirm eligibility, and for performance of the c-MET biomarker analysis. c-MET biomarker results determined the subgroup placement for data analysis as follows: c-MET positive (n=46), c-MET negative (n=47), and c-MET unknown (n=16).

Overall Study

Analysis population for the primary outcome, as defined in the registry: ORR was assessed on the efficacy analysis set, consisting of all patients with measurable disease, PRCC confirmed by a central laboratory and have received at least 1 dose of AZD6094 (n = 85).

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: All subjects who received at least one dose of AZD6094 are included in the baseline analysis.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (RECIST Version 1.1), measured over Up to 12 months.

The primary endpoint, objective response rate (ORR), is the proportion of participants whose tumors were assessed as having either a complete response or a partial response. In this trial, response was assessed by the investigator using Response Evaluation Criteria for Solid Tumours (RECIST) version 1.1. The timeframe was up to 12 months.

ORR is used in oncology trials to summarize tumor response among participants with disease that can be measured. A proportion is more interpretable when its analysis population is defined, because eligibility for response assessment depends on having measurable disease and satisfying the stated diagnostic and treatment criteria. In this record, the efficacy analysis set consisted of participants with measurable disease, PRCC confirmed by a central laboratory, and at least 1 dose of AZD6094; the set is reported as n = 85.

As a statistical measure, an observed response proportion would describe the frequency of qualifying responses in that analysis set. Its precision would depend on the number of participants assessed and the number meeting the response definition. A confidence interval, if reported, would express uncertainty around that proportion; the registry record does not report such an interval or the response count.

ORR does not by itself describe how long a response lasts, whether disease control persists, or how outcomes compare with another treatment. The registry lists duration of response and time-to-event outcomes among secondary measures, but their results are not reported in the registry record. The primary endpoint definition is available; its observed value and precision are not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies an investigator-assessed binary primary outcome: participants are classified by whether they had a complete or partial response under RECIST version 1.1. A binary outcome records whether an event or condition occurred, rather than measuring a continuous quantity such as tumor size. The corresponding summary would ordinarily be a response count and proportion within the defined analysis population. The record gives the definition and population, but does not report the count or proportion.

What does a confidence interval describe?

General statistical explanation: a confidence interval communicates uncertainty around an estimate. For a response proportion, it would indicate how much sampling uncertainty remains around the observed value, under the method used to construct the interval. A narrow interval suggests greater precision than a wide interval, but neither width nor location can be assessed without an interval and estimate. Neither is reported for the primary outcome in the registry record.

An interval would not correct limitations in the design. It quantifies uncertainty under a statistical model; it does not create a control group, remove possible assessment bias, or make an investigator-assessed outcome equivalent to a blinded assessment. A precise estimate from a single group remains an estimate of outcomes in that group, not a randomized comparison with another treatment.

Why does the analysis population matter?

The primary outcome population is stated as participants with measurable disease, central confirmation of PRCC, and at least 1 dose of AZD6094. This definition determines whose outcomes contribute to the endpoint. A response proportion calculated using a different population could answer a different question. The registry's enrollment figure of 111 and efficacy analysis set of n = 85 therefore describe different trial populations; the registry does not report the participant-level reasons for that distinction.

The treatment-naïve and previously treated groups are both described as eligible, but the record does not give separate primary response estimates for those groups. It also does not report a prespecified subgroup analysis for treatment history. Results should not be inferred for either subgroup from the overall design description.

What can a single-arm estimate establish?

General statistical explanation: an outcome rate in one group describes what was observed among participants receiving the intervention under the study conditions. A comparison with an appropriate control group is ordinarily needed to estimate a relative treatment effect while accounting for differences in underlying risk and other influences. With no concurrent comparator, changes in disease course, participant selection, supportive care, and measurement can contribute to observed outcomes. This is why the design cannot establish a randomized comparative effect.

Open-label status is relevant to endpoint measurement. ORR was based on investigator assessment. RECIST version 1.1 supplies a structured response definition, but the registry record does not report a blinded central review of the primary response outcome. Standardized criteria can support consistent classification; they do not remove all potential influence of unmasked assessment.

How should planning calculations be read?

General statistical explanation: a sample-size calculation is a planning exercise based on assumptions about the effect to detect, significance level, allocation, and statistical method. It is not a description of the result actually observed in a trial. Any sample-size figures accompanying a planning illustration are hypothetical planning quantities, not observed power and not the trial's original design justification. The stated illustration assumptions are two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the target effect set as a stated fraction of an observed effect. That hypothetical two-arm setup is distinct from this single-arm trial. The registry record does not report the trial's own sample-size justification.

Likewise, a calculation based on posted summary statistics, if labeled recalculated, would be an unadjusted re-calculation rather than the sponsor's analysis. No recalculated primary endpoint result is reported in the registry record. If recalculated results and sponsor results disagree, the sponsor's own analysis takes precedence.

What statistical details are unavailable?

The registry record does not report the primary response estimate, its confidence interval, a p-value, or the detailed statistical method used for the primary endpoint. It also does not report an adjustment for covariates, a model for the primary endpoint, or an interim analysis plan. These absences mean readers cannot reconstruct or evaluate the endpoint analysis from the registry description alone. General statistical concepts can clarify what such methods would mean, but they cannot fill in trial-specific procedures that are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures, including ORR and several secondary outcomes. Multiple outcomes can raise a multiplicity question: when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and structure of tests. This is a general statistical concern, not evidence that a particular adjustment was used or needed for a reported claim in this trial.

The registry record does not report a multiplicity-control strategy, a hierarchy of confirmatory outcomes, or a detailed statistical analysis plan. It also lists no analyses. Therefore, the record does not establish which outcomes were treated as confirmatory, whether subgroup analyses were adjusted, or how results across endpoints were intended to be interpreted. The presence of numerous listed measures alone does not establish that all were formally tested.

Missing-data handling is also not reported in the registry record. The efficacy population definition specifies measurable disease, central confirmation, and receipt of at least 1 dose, but it does not explain how unavailable tumor assessments, withdrawals, or other missing endpoint data were handled. No imputation approach, missingness assumptions, or sensitivity analysis is described. These details matter because the handling of unobserved outcomes can affect an estimated response proportion.

The record distinguishes the efficacy analysis set from the enrolled population but does not report a full accounting of participant flow or reasons for exclusion from that set. It also does not report whether the primary outcome analysis used any additional exclusions. Accordingly, readers should not assume that missing outcomes were counted as nonresponses or handled in another particular way.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute kidney injury (3.7%), anaemia (2.8%), ascites (1.8%), constipation (1.8%), abdominal incarcerated hernia (0.9%).

The registry reports a safety group titled AZD6094 600 mg Per Day Orally. For serious adverse events, 109 participants are listed as at risk and 27 as affected. For other adverse events, 109 are listed as at risk and 107 as affected. The record also lists 57 deaths. These are separate registry figures and should not be combined into a single event count; the number affected is not the same as the total number of adverse events.

The listed serious adverse event terms and percentages are acute kidney injury, 3.7%; anaemia, 2.8%; ascites, 1.8%; constipation, 1.8%; abdominal incarcerated hernia, 0.9%; and abdominal pain, 0.9%. These are reported term-level percentages. A participant may experience more than one event, so percentages for separate terms should not be added to infer a total. The registry record does not provide further detail about timing, duration, severity grading, or causal attribution for these terms.

These safety figures are descriptive observations in a single treatment group. Without a concurrent control group, they do not establish how frequently the events would have occurred in the absence of AZD6094. The listed deaths are not identified in the record as caused by treatment, and the registry record does not report a causal assessment in this summary.

12. What the Result Does, and Does Not, Mean

The record describes a phase II investigation of continuously administered AZD6094 in patients with PRCC, with ORR as the primary endpoint. It defines response using complete or partial response by investigator assessment under RECIST version 1.1, and defines an efficacy analysis set of n = 85. It also provides descriptive safety counts and lists secondary outcomes.

However, the primary response result is not reported in the registry record. Without the response count, estimated proportion, or a measure of precision, the record does not show how often an objective response occurred or how uncertain an estimate would be. The design and endpoint definition alone cannot establish the observed result.

The single-arm, open-label structure also limits what an outcome could mean. An observed response in the AZD6094 group would describe that group under the trial's assessment conditions. It would not, by itself, show the difference between AZD6094 and another treatment, nor isolate the contribution of the intervention from other influences. A randomized comparison is not reported.

The registry's listed secondary outcomes do not fill the primary-result gap. Results for progression-free survival, overall survival, tumor-size change, duration of response, and peak plasma concentration are not reported in the registry record. Nor are the listed c-MET-stratified survival outcomes accompanied by estimates in this record.

The safety counts likewise describe events recorded in the treatment group but do not establish comparative risk or causal attribution. Taken together, the record supports understanding of the trial's question, population, intervention, and some safety reporting. It does not support a conclusion about the size, precision, or comparative meaning of the primary efficacy result.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design determines the question an estimate can answer. The study enrolled patients with PRCC and evaluated AZD6094 in a single group. Its primary endpoint was a defined response measure, but no control group was included. That makes the central inferential distinction important: describing outcomes among treated participants is not the same as estimating a comparative treatment effect.

The record also illustrates why the analysis population must accompany an endpoint. The overall enrollment and the efficacy analysis set are reported separately, and the latter has specific disease, measurement, and treatment-entry criteria. Interpretation of any response proportion depends on knowing which participants contributed to its numerator and denominator.

Assessment procedures matter as well. RECIST version 1.1 gives a structured framework for classifying response, while investigator assessment in an open-label study leaves a different set of potential measurement concerns than a masked independent assessment. The registry record does not describe a blinded independent primary response review.

Finally, the difference between an outcome being listed and a result being reported is central to statistical reading. The registry specifies multiple outcomes and safety terms, but it does not give the primary response estimate or detailed analysis methods. Recognizing that boundary prevents design information, enrollment figures, or endpoint definitions from being mistaken for evidence about the outcome itself.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

A major trial-specific limitation in interpreting the registry record is that it does not report the primary ORR result. The response count, proportion, and uncertainty interval are absent, so the primary endpoint cannot be numerically evaluated from this record. Results for the listed secondary efficacy outcomes are also not reported.

The single-arm design has no concurrent comparator, and the study was open-label. Therefore, the design does not support a randomized comparison, while investigator assessment of response may be subject to measurement influences associated with unmasked assessment. The registry record does not report a blinded independent review of the primary response endpoint.

The record gives enrollment of 111 and an efficacy analysis set of n = 85, but does not provide a participant-flow account explaining the distinction. It does not report the handling of missing tumor assessments, withdrawals, or other unavailable endpoint data. The detailed analysis plan, trial-specific sample-size justification, and multiplicity strategy are also not reported in the registry record.

Although the study description includes both treatment-naïve and previously treated patients, subgroup response results by treatment history are not reported. Similarly, secondary survival outcomes are listed by c-MET status, but their estimates and analysis details are absent. These limitations restrict interpretation of both the overall efficacy question and potential subgroup patterns.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase II Trial to Evaluate the Efficacy of AZD6094 (HMPL-504) in Patients With Papillary Renal Cell Carcinoma (PRCC) — NCT02127710.
• Registry record last updated 2021-04-19; status last verified 2021-03.
• Results first posted 2017-10-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT02127710 is a completed, open-label, single-arm phase II study sponsored by AstraZeneca. It evaluated AZD6094 600 mg by mouth once daily continuously in patients with papillary renal cell carcinoma who were treatment naïve or previously treated. The registry records enrollment of 111.

The primary endpoint was investigator-assessed objective response rate under RECIST version 1.1, over up to 12 months. The efficacy analysis set consisted of participants with measurable disease, central confirmation of PRCC, and at least 1 dose; it is reported as n = 85. The registry record does not report the observed primary response result or its precision.

Secondary measures include survival, tumor-size change, duration of response, and peak plasma concentration. The record also lists serious and other adverse event figures. Detailed analysis methods, missing-data procedures, multiplicity handling, and the trial's sample-size justification are not reported in the registry record.